EA200601461A1 - NEW DERIVATIVES BENZIL (IDEN) LACTAM - Google Patents

NEW DERIVATIVES BENZIL (IDEN) LACTAM

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Publication number
EA200601461A1
EA200601461A1 EA200601461A EA200601461A EA200601461A1 EA 200601461 A1 EA200601461 A1 EA 200601461A1 EA 200601461 A EA200601461 A EA 200601461A EA 200601461 A EA200601461 A EA 200601461A EA 200601461 A1 EA200601461 A1 EA 200601461A1
Authority
EA
Eurasian Patent Office
Prior art keywords
lactam
benzil
iden
compounds
formula
Prior art date
Application number
EA200601461A
Other languages
Russian (ru)
Inventor
Майкл Аарон Бродни
Стефан Карон
Кристофер Дж. Хелал
Джеффри У. Раггон
Йонг Тао
Нга М. До
Original Assignee
Пфайзер Продактс, Инк.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Пфайзер Продактс, Инк. filed Critical Пфайзер Продактс, Инк.
Publication of EA200601461A1 publication Critical patent/EA200601461A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34—Tobacco-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C07D211/76—Oxygen atoms attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings

Abstract

Настоящее изобретение относится к новым производным бензил(иден)лактама, соединениям формулы I, где Rпредставляет собой группу формулы Gили G, изображенной ниже, где R, R, R, R, X, а, n и m являются такими, как определено здесь, их фармацевтически приемлемым солям и фармацевтическим композициям, которые включают в себя селективные антагонисты, обратные агонисты и частичные агонисты серотониновых рецепторов 1 (5-HT), а именно одного или обоих 5-HTи 5-HTрецепторов. Соединения по изобретению являются полезными в лечении или предупреждении депрессии, тревоги, обсессивно-компульсивного расстройства (OCD) и других расстройств, при которых показан агонист или антагонист 5-HT, и имеют сниженный потенциал сердечных побочных эффектов, в частности пролонгирования QTc.The present invention relates to new benzyl (Eden) lactam derivatives, compounds of the formula I, wherein R is a group of the formula G or G shown below, where R, R, R, R, X, a, n and m are as defined herein, their pharmaceutically acceptable salts and pharmaceutical compositions, which include selective antagonists, inverse agonists and partial agonists of serotonin receptors 1 (5-HT), namely one or both 5-HT and 5-HT receptors. The compounds of the invention are useful in the treatment or prevention of depression, anxiety, obsessive-compulsive disorder (OCD) and other disorders in which a 5-HT agonist or antagonist is indicated and have a reduced potential for cardiac side effects, in particular QTc prolongation.

EA200601461A 2004-03-17 2005-03-07 NEW DERIVATIVES BENZIL (IDEN) LACTAM EA200601461A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US55380804P 2004-03-17 2004-03-17
PCT/IB2005/000583 WO2005090300A1 (en) 2004-03-17 2005-03-07 Novel benzyl(idene)-lactam derivatives

Publications (1)

Publication Number Publication Date
EA200601461A1 true EA200601461A1 (en) 2007-02-27

Family

ID=34960867

Family Applications (1)

Application Number Title Priority Date Filing Date
EA200601461A EA200601461A1 (en) 2004-03-17 2005-03-07 NEW DERIVATIVES BENZIL (IDEN) LACTAM

Country Status (29)

Country Link
US (1) US7479559B2 (en)
EP (1) EP1727794B1 (en)
JP (1) JP4880583B2 (en)
KR (1) KR20060124770A (en)
CN (1) CN1934081A (en)
AP (1) AP2006003726A0 (en)
AR (1) AR050403A1 (en)
AT (1) ATE533745T1 (en)
AU (1) AU2005223481A1 (en)
BR (1) BRPI0508825A (en)
CA (1) CA2559530C (en)
CR (1) CR8618A (en)
DO (1) DOP2005000035A (en)
EA (1) EA200601461A1 (en)
EC (1) ECSP066853A (en)
ES (1) ES2374629T3 (en)
GT (1) GT200500051A (en)
IL (1) IL178105A0 (en)
MA (1) MA28474B1 (en)
NL (1) NL1028558C2 (en)
NO (1) NO20063602L (en)
PA (1) PA8626501A1 (en)
PE (1) PE20051153A1 (en)
SV (1) SV2005002051A (en)
TN (1) TNSN06287A1 (en)
TW (1) TW200604165A (en)
UY (1) UY28811A1 (en)
WO (1) WO2005090300A1 (en)
ZA (1) ZA200607133B (en)

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EP1836164B1 (en) * 2005-01-13 2011-08-24 GE Healthcare Limited 11c-labeled benzyl-lactam compounds and their use as imaging agents
CA2612268A1 (en) * 2005-06-17 2006-12-28 Pfizer Products Inc. Metabolites of 1-[6-(1-ethyl-1-hydroxy-propyl)-pyridin-3-yl]-3-[2-(4-methyl-piperazin-1-yl)-benzyl]-pyrrolidin-2-one as seratonin receptor antagonists
WO2007026219A2 (en) * 2005-08-31 2007-03-08 Pfizer Products Inc. Combinations of a 5-ht1b antagonist with a noradrenalin re-uptake inhibitor or a serotonin noradrenalin reutake inhibitor for treating cns conditions
WO2008068614A2 (en) * 2006-12-06 2008-06-12 Pfizer Products Inc. Stereoselective synthesis of 1-[6-ethyl-1,2-dihydroxy-propyl)-pyridin-3-yl]-3-[2-(4-methyl-piperazin-1-yl)-benzyl]-pyrrolidin-2-one
FR2948660B1 (en) * 2009-07-30 2011-08-19 Oroxcell 2-AMINO-2-PHENYL-ALKANOL DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
EP2338873A1 (en) 2009-12-22 2011-06-29 Gmeiner, Peter New aminotetraline derivatives
WO2011075784A1 (en) * 2009-12-23 2011-06-30 Peter Maccallum Cancer Institute Compounds, preparations and uses thereof
WO2014028829A1 (en) 2012-08-16 2014-02-20 The Scripps Research Institute Novel kappa opioid ligands
JP6440625B2 (en) 2012-11-14 2018-12-19 ザ・ジョンズ・ホプキンス・ユニバーシティー Methods and compositions for treating schizophrenia
JP6321825B2 (en) * 2014-01-20 2018-05-09 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ N-phenyl-lactam derivatives capable of stimulating neurogenesis and their use in the treatment of neurological disorders
TW201706265A (en) 2015-03-09 2017-02-16 必治妥美雅史谷比公司 Lactams as inhibitors of ROCK
WO2020183011A1 (en) 2019-03-14 2020-09-17 Institut Curie Htr1d inhibitors and uses thereof in the treatment of cancer

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Publication number Publication date
US20050245521A1 (en) 2005-11-03
UY28811A1 (en) 2005-10-31
ECSP066853A (en) 2006-11-24
EP1727794A1 (en) 2006-12-06
PE20051153A1 (en) 2006-01-28
ATE533745T1 (en) 2011-12-15
US7479559B2 (en) 2009-01-20
NL1028558A1 (en) 2005-09-20
AR050403A1 (en) 2006-10-25
GT200500051A (en) 2005-10-24
CN1934081A (en) 2007-03-21
DOP2005000035A (en) 2005-10-31
CR8618A (en) 2006-11-15
SV2005002051A (en) 2005-12-13
EP1727794B1 (en) 2011-11-16
JP4880583B2 (en) 2012-02-22
CA2559530C (en) 2012-04-24
NO20063602L (en) 2006-09-08
TW200604165A (en) 2006-02-01
PA8626501A1 (en) 2005-11-25
CA2559530A1 (en) 2005-09-29
AP2006003726A0 (en) 2006-10-31
TNSN06287A1 (en) 2007-12-03
BRPI0508825A (en) 2007-08-14
JP2007529495A (en) 2007-10-25
KR20060124770A (en) 2006-12-05
MA28474B1 (en) 2007-03-01
ZA200607133B (en) 2007-12-27
IL178105A0 (en) 2006-12-31
AU2005223481A1 (en) 2005-09-29
ES2374629T3 (en) 2012-02-20
NL1028558C2 (en) 2006-06-27
WO2005090300A1 (en) 2005-09-29

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